Human iPS cells have been established (see for example Non-Patent Document 1 and Patent Document 1), and hold promise in the field of regenerative medicine. iPS cells, also called artificial pluripotent stem cells or induced pluripotent stem cells, are cells with acquired pluripotency, and these cells acquire pluripotency by the introduction of genes coding for various kinds of transcription factors, such as Oct family (Oct3/4), Sox family (Sox2, Sox1, Sox3, Sox15, Sox 17, etc.), Klf family (Klf4, Klf2, etc.), Myc family (c-Myc, N-Myc, L-Myc, etc.), Nanog and LIN28 transcription factors, that confer pluripotency on somatic cells (such as fibroblasts for example).
Cells that are known to be pluripotent include ES cells as well as iPS cells, but with ES cells there are problems of bioethics because the cells are obtained from pre-implantation stage embryos, hence there have been problems in using such cells in regenerative medicine. Such problems can be avoided with iPS cells because they can be established from skin and cells, which are relatively easy to obtain. Moreover, iPS cells also hold promise for advancing regenerative medicine because they can be obtained from the tissue of a patient requiring treatment, thus eliminating the risk of immune rejection.
Recently, attempts have been made in the fields of dentistry and orthopedic surgery to induce differentiation of iPS cells into osteoblasts, which can then be used to regenerate alveolar bone and cartilage. In the dental field for example, dental implant treatment and prosthodontic treatment are often difficult in cases of patients who have lost teeth, due to bone loss in the jaw. In such cases, implantation and the like can be accomplished if osteoblasts are transplanted to the area of bone loss in the jaw, and used to regenerate alveolar bone. Osteoblasts obtained by inducing differentiation of iPS cells established from somatic cells of the same patient do not pose a risk of immune rejection. Moreover, the inventors have confirmed that the efficiency of iPS cell establishment is extremely high using oral epithelial cells and oral fibroblasts (see for example Patent Document 2).
Because iPS cells are pluripotent, however, there have been serious problems with tumorigenesis after implantation. Methods that have been proposed for solving this problem include a method using iPS cell tumorigenesis markers to sort and remove tumorigenic cells (see for example Non-Patent Document 2), and a method using iPS cells that have been directed to the target tissue in vitro, in which the cells are cell sorted by FACS or the like, and target cells are selected and used in transplantation. However, drawbacks of these methods include the difficulty of securing adequate numbers of cells, and the risk of contamination.
Thus, iPS cells hold promise in the field of regenerative medicine, but because of such problems they have yet to be put into practical use. That is, the challenge for achieving clinical application of iPS cells is to find ways of suppressing tumorigenesis.
Meanwhile, HMG-CoA reductase inhibitors (statins) are in wide clinical use to treat high cholesterol by inhibiting cholesterol synthesis. In recent years, it has been confirmed that statins have diverse pharmacological effects on differentiation and proliferation of various cells. However, it was not known that tumorigenesis could be suppressed by culturing iPS cells in the presence of statins.    Non-Patent Document 1: Takahashi K. et al. (2007), “Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors”, Cell 131:861-872.    Non-Patent Document 2: Tang C et al., “An antibody against SSEA-5 glycan on human pluripotent stem cells enables removal of teratoma-forming cells”, Nat. Biotechnol. 2011; 29(9):829-34.    Patent Document 1: WO 2007/069666    Patent Document 2: WO 2011/024550